Hydrochloric Acid → HCID 66732390, compound

HRID 1963133Notes

Reaction equation

HRID 1963133 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CC(OC)(C)C.Cl[Pd]Cl>[ClH:1].[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 2736842Methyl 2-chloropyridine-4-carboxylate

Product 1

HCID 66732390HCID 66732390, compoundYield 91.2%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (4.5 g, 26.23 mmol), 4-fluorophenylboronic acid (4.51 g, 32.26 mmol), potassium carbonate (2.247 g, 16.26 mmol) and PdCl2 (dppf) (0.380 g, 0.52 mmol) were mixed in methanol (30 mL) in two 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. The solids were removed by filtration and the filtrate evaporated to yield a dark red slurry. To the residue was added HCl (1.25 M in methanol, 100 mL). The mixture was stirred at 45° C. for 4 h, then concentrated. Satd NaHCO3 (100 mL) was added under ice cooling and extracted with DCM (3×100 mL) The combined organic phases were washed with brine, passed through a phase separator and evaporated to yield a brown solid. The crude was dissolved in MTBE (180 mL) and some solids were filtered off. Cooled with ice-water, hydrogen chloride (4 M in dioxane, 10 mL, 40 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at 0° C. for 10 min. The solid was collected by filtration and washed with MTBE to yield methyl 2-(4-fluorophenyl)isonicotinate hydrochloride (6.4 g, 91%) as a beige solid. 1H NMR (400 MHz, cd3od) d 4.07 (s, 3H), 7.37-7.51 (m, 2H), 8.02-8.13 (m, 2H), 8.37 (dd, 1H), 8.71 (d, 1H), 8.97 (dd, 1H). MS m/z 232 (M+H)+

Workup

  1. customThe vials were capped
  2. customThe solids were removed by filtration
  3. customthe filtrate evaporated
  4. customto yield a dark red slurry
  5. concentrationconcentrated
  6. additionSatd NaHCO3 (100 mL) was added under ice cooling
  7. extractionextracted with DCM (3×100 mL) The combined organic phases
  8. washwere washed with brine
  9. customevaporated
  10. customto yield a brown solid
  11. filtrationsome solids were filtered off
  12. additionwas added dropwise
  13. stirringduring stirring
  14. customa suspension was formed
  15. stirringThe suspension was stirred at 0° C. for 10 min
  16. filtrationThe solid was collected by filtration
  17. washwashed with MTBE

Sources & evidence

ORD record
ord-9061cc394fa24eddb02e4b74ba0fc311
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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